Studies on the synthesis of croomine: Synthesis of the tricyclic B,C,D-ring core structure

Article abstract of DOI:10.1055/s-2004-817773

A convergent and asymmetric synthesis of the tricyclic B,C,D-ring core structure of croomine has been achieved, using aminolysis reactions of chiral vinyl epoxides and the RCM reaction.

Full text of DOI:10.1055/s-2004-817773

LETTER
779
Studies on the Synthesis of Croomine: Synthesis of the Tricyclic B,C,D-Ring
Core Structure
Synthesis of the
T
r
a
icyclic B,C
r
,D-Ring
l
Core Structu
B
re . Lindsay, Stephen G. Pyne*
Department of Chemistry, University of Wollongong, Wollongong, New South Wales, 2522, Australia
Fax +61(2)42214287; E-mail: Stephen_Pyne@uow.edu.au
Received 17 December 2003
domestic animals.1 The biological activities and the struc-
Abstract: A convergent and asymmetric synthesis of the tricyclic
B,C,D-ring core structure of croomine has been achieved, using
aminolysis reactions of chiral vinyl epoxides and the RCM reaction.
tural diversity and relative complexity of these alkaloids
has attracted the attention of many synthetic chemists.
Their efforts have resulted in the total synthesis of several
Stemona alkaloids4 and the publication of model synthetic
studies.5
Key words: oxazolindone, pyrrolidine, ring-closing metathesis,
azepine, Stemona alkaloid
We report here our efforts to develop a convergent synthe-
sis of the tricyclic B,C,D-ring core structure of croomine
(1) based on the retro-synthetic analysis shown in
Scheme 1. Our analysis suggested that the A and D rings
could be prepared by an oxidative lactonization reaction
of the tetrol 2, while the B-ring could be secured via a N-
alkylation reaction. Compound 2 could be obtained from
the diene 3 via a ring-closing metathesis reaction.6,7 The
diene 3 should be available from an epoxide-aminolysis
reaction between the vinyl epoxides 4 or 7 and the allylic
amines 5 and 6, respectively.6,8,9
The Stemona group of alkaloids includes more than 40
different natural products that have been structurally clas-
sified into five different groups.1 The pyrrolo[1,2-
a]azepine (1-azabicyclo[5.3.0]decane) nucleus is com-
mon to all compounds in these groups. A few of these al-
kaloids do not fit these five structural groups and have a
more complex bridged structure or ring structures that
most likely arise from initial oxidative cleavage of the
pyrrolo[1,2-a]azepine ring system.1 In 2003 we reported
the structure of stemocurtisine, the first example of a
Stemona alkaloid with a pyrido[1,2-a]azepine A,B-ring
system, isolated from the roots of S. curtisii.2 Later in that
year Hofer and Greger reported the isolation of four other
Stemona alkaloids with the pyrido[1,2-a]azepine A,B-
ring system plus stemocurtisine.3 These alkaloids repre-
sent a new and sixth structural group for Stemona alka-
loids. Extracts of the roots of Stemona species have been
used in traditional Chinese medicine for the treatment of
various respiratory diseases and as anthelmintic agents for
As model studies to test the viability of our proposed
synthesis we have prepared the chiral allylic amine 11, a
structurally simpler analogue of 6, and the vinyl epoxide
12, the nor-methyl analogue of 7, and used them as build-
ing blocks to prepare a molecule having the tricyclic
B,C,D-ring core structure of croomine (1). Compound 11
was prepared from the chiral cis-epoxide 9 (ee 92–94%),
which was readily available in 5 steps (38% overall)
from the known PMB protected 5-hexyn-1-ol 810 using
RCM
Me
A
Me
Me
PO
O
HO
H
H
H
a) [O]
C
N
a
Me
Me
OH
Me
OP
O
HO
b) N-alkylation
D
HO
N
N
H
B
H
H
H
H
H
H
O
OH
OP1
HO
b
O
a
OP1
croomine 1
2
3
Me
O
Me
PO
OH
H
H
H
H2N
OH
PO
Me
OP
OR
Me
OP
+
+
H
H
NH2
O
H
5
7
OP1
OP1
4
6
Scheme 1 Retrosynthetic analysis of croomine (1).
SYNLETT 2004, No. 5, pp 0779–0782
0
2.
0
4.
2
0
0
4
Advanced online publication: 10.02.2004
DOI: 10.1055/s-2004-817773; Art ID: D30003ST.pdf
© Georg Thieme Verlag Stuttgart · New York

780
K. B. Lindsay, S. G. Pyne
LETTER
chemistry already described by us (Scheme 2).8,9 Aminol- Heating a mixture of 11 and 12 and lithium triflate (1.5
ysis of 9 as a suspension in aqueous ammonia (28%) in a equiv) in MeCN solution at 130 °C for 4 days in a sealed
sealed Teflon vessel with heating in a microwave reactor tube provided the amino alcohol 13 (78%, ee estimated ca.
(Milestone, ETHOS SEL microwave labstation)6 at 110 95% due to removal of most of the undesired enantiomers
°C for 30 minutes, with strict temperature control, gave of 11 and 12 as the diastereomer of 13, but not de-
regioselectively, the amino alcohol 10 in 98% yield which termined) and its diastereomer (not shown, 17%) that
was converted to its corresponding O-TBS ether 11 in were readily separated by column chromatography
85% yield as a single diastereomer (Scheme 2). The chiral (Scheme 3).6 The latter compound arises from the reac-
epoxide 12 was prepared as previously described from tion of ent-11 with 12 and 11 with ent-12. Treatment of 13
this laboratory.8
with triphosgene at –40 °C in the presence of base (Et3N)
gave the oxazolidinone 14 in 84% yield, along with an
aziridine (not shown, 14%) that arises from reaction of
triphosgene with the secondary hydroxyl group of 13 fol-
lowed by intramolecular SN2 displacement by the nitrogen
atom at the carbon bearing the activated hydroxyl. The
low temperature was required to minimize the formation
of this aziridine. The oxazolidinone 14 was treated under
standard RCM conditions (Grubbs’ 1st generation catalyst
and high dilution in CH2Cl2 solution).7,11 The reaction was
slow requiring 7 days of heating at reflux and high catalyst
loading (50 mol%), however the yield of the 2,5-dihydro-
pyrrole 15 was excellent (93%). Catalytic hydrogenation
of the alkene group in 15 smoothly gave the pyrrolidine 16
O
RO
a, b
5-steps
NH2
H
(36 % overall)
OPMB
OPMB
OPMB
8
9
10, R = H
11, R = TBS
Scheme 2 Reagents: (a) aqueous ammonia (28%), 110 °C, 30 min,
microwave heating (98%). (b) TBSCl, imidazole, MeCN, r.t. (85%).
H
H
TBSO
a
TBSO
b
c
+
11
H
N
N
O
H
H
O
H
H
OH
O
OTBS
OTBS
OTBS
12
OPMB
OPMB
14
13
H
H
O
H
TBSO
TBSO
TBDPSO
d
e–g
h
N
O
N
H
N
H
H
H
O
TBDPSO
OTBS
OTBS
OTBDPS
O
OPMB
OPMB
16
OPMB
17
15
H
H
H
HO
j
TBDPSO
TBDPSO
i
k
N
N
N
H
H
H
H
H
OH
TBDPSO
OTBDPS
OH
OTBDPS
TBDPSO
20
OH
19
18
1
H
3
H
H
H
H
O
H
HO
9
N
N
N
O
H
O
H
O
H
O
5
O
O
O
22
23
21
Scheme 3 Reagents (a) LiOTf, CH3CN, 130 °C, 4 d (95%); (b) triphosgene, NEt3, CH2Cl2, –40 °C (84%); (c) Grubbs’ cat., CH2Cl2, reflux, 7
d (93%); (d) Pd/C, H2, EtOAc, r.t., 1 h (95%); (e) n-Bu4NF, THF, r.t. (100%); (f) NaOH, MeOH, H2O, 100 °C, microwave, 90 min (93%); (g)
TBDPSCl, imidazole, CH3CN, 75 °C, 2 d (81%); (h) CAN, CH3CN, H2O, CH2Cl2 (93%); (i) PPh3, CBr4, Et3N, 0 °C to r.t. (81%); (j) HCl (38%),
MeOH, CHCl3, 90 °C, 3 d (84%); (k) TEMPO, BAIB, HOAc, r.t. (28%).
Synlett 2004, No. 5, 779–782 © Thieme Stuttgart · New York

LETTER
Synthesis of the Tricyclic B,C,D-Ring Core Structure
781
Org. Chem. 1993, 58, 3840. (d) Wipf, P.; Kim, Y.;
Goldstein, D. M. J. Am. Chem. Soc. 1995, 117, 11106.
without loss of the PMB group. Attempts to remove the
PMB group from the analogous tris-TBS analogue of 17
resulted in cleavage of the primary TBS group and hence
16 was treated first with tetra-n-butylammonium fluoride
(TBAF) to give the corresponding diol, which upon base-
catalyzed hydrolyses of the oxazolidinone group and
finally O-silylation with tert-butylchlorodiphenylsilane
(TBDPSCl) gave the pyrrolidine 17 in 75% overall yield.
The primary O-PMB group was removed under oxidative
conditions using ceric ammonium nitrate (CAN) to give
the primary alcohol 18 in 93% yield which was converted
to the 1H-pyrrolo[1,2-a]azepine 19 in 81% yield under
standard cyclization conditions.8,12 Compound 19 was
treated with aqueous hydrochloric acid to give the triol
20.13 Oxidation of this triol to give the corresponding
keto-lactone 23 proved difficult. For example, the use of
tetrapropylammoniumperruthenate (TPAP)–N-methyl-
morpholine-N-oxide (NMO), a reagent combination that
we have used successfully before to prepare a lactone
from a related 1,4-diol,6 gave a mixture of products in-
cluding ones that showed aldehyde signals in the 1H NMR
spectra. When the oxidizing system 2,2,6,6-tetramethyl-
1-piperidinyloxyl (TEMPO, catalytic)–bis-acetoxy iodo-
benzene (BAIB, stoichiometric)14,15 was employed in
HOAc as solvent, the product 22 was isolated in 28%
yield having a novel 5,9-epoxy-1H-pyrrolo[1,2-a]azepine
tricyclic ring structure. This structure most likely arises
from oxidation of the tertiary amine to the corresponding
cyclic iminium ion 21 followed by ring closure through
the secondary hydroxyl in the azepine ring. The structure
of 22 was supported by COSY, 13C/DEPT and HSQC
NMR experiments and mass spectrometry.14 The hemi-
aminal carbon (C-5) was evident as a methine carbon at 96
ppm in the 13C/DEPT NMR spectra.
(e) Martin, S. F.; Barr, K. J. J. Am. Chem. Soc. 1996, 118,
3299. (f) Morimoto, Y.; Iwahashi, M.; Bishida, K.; Hayashi,
Y.; Shirahama, H. Angew. Chem Int. Ed. Engl. 1996, 35,
904. (g) Jacobi, P. A.; Lee, K. J. Am. Chem. Soc. 1997, 119,
3409. (h) Kende, A. S.; Smalley, T. L. Jr.; Huang, H. J. Am.
Chem. Soc. 1999, 121, 7431. (i) Martin, S. F.; Barr, K. J.;
Smith, D. W.; Bur, S. K. J. Am. Chem. Soc. 1999, 121, 6990.
(j) Jacobi, P. A.; Lee, K. J. Am. Chem. Soc. 2000, 122, 4295.
(k) Williams, D. R.; Fromhold, M. G.; Earley, J. D. Org.
Lett. 2001, 3, 2721. (l) Kende, A. S.; Martin Hernando, J. I.;
Milbank, J. B. J. Org. Lett. 2001, 3, 2505. (m) Morimoto,
Y.; Iwahashi, M.; Kinoshita, T.; Nishida, K. Chem.–Eur. J.
2001, 7, 4107. (n) Kende, A. S.; Martin Hernando, J. I.;
Milbank, J. B. J. Tetrahedron 2002, 58, 61. (o) Wipf, P.;
Rector, S. R.; Takahashi, H. J. Am. Chem. Soc. 2002, 124,
14848. (p) Ginn, J. D.; Padwa, A. Org. Lett. 2002, 4, 1515.
(q) Bruggemann, M.; McDonald, A. I.; Overman, L. E.;
Rosen, M. D.; Schwink, L.; Scott, J. P. J. Am. Chem. Soc.
2003, 125, 15284. (r) Williams, D. R.; Shamim, K.; Reddy,
J. P.; Amato, G. S.; Shaw, S. M. Org. Lett. 2003, 5, 3361.
(5) (a) Xiang, L.; Kozikowski, A. P. Synlett 1990, 279.
(b) Morimoto, Y.; Iwahashi, M. Synlett 1995, 1221.
(c) Rigby, J. H.; Laurent, S.; Cavezza, A.; Heeg, M. J. J. Org.
Chem. 1998, 63, 5587. (d) Wipf, P.; Li, W. J. Org. Chem.
1999, 64, 4576. (e) Jung, S. H.; Lee, J. E.; Joo, H. J.; Kim
Sang, H.; Koh, H. Y. Bull. Kor. Chem. Soc. 2000, 21, 159.
(f) Rigby, J. H. Synlett 2000, 1. (g) Hinman, M. M.;
Heathcock, C. H. J. Org. Chem. 2001, 66, 7751.
(h) Velázquez, F.; Olivo, H. F. Org. Lett. 2002, 4, 3175.
(i) Boren, B.; Hirschi, J. S.; Reibenspies, J. H.; Tallant, M.
D.; Singleton, D. A.; Sulikowski, G. A. J. Org. Chem. 2003,
68, 8991.
(6) Lindsay, K. B.; Tang, M.; Pyne, S. G. Synlett 2002, 731.
(7) Davis, A. S.; Gates, N. J.; Lindsay, K. B.; Tang, M.; Pyne, S.
G. Synlett 2004, 6, 49.
(8) Lindsay, K. B.; Pyne, S. G. J. Org. Chem. 2002, 67, 7774.
(9) Tang, M.; Pyne, S. G. J. Org. Chem. 2003, 68, 7818.
(10) Hayashi, N.; Fujiwara, K.; Murai, A. Tetrahedron 1997, 53,
12425.
In conclusion, we have developed a convergent and asym-
metric synthesis of the tricyclic B,C,D-ring core structure
of croomine, using aminolysis reactions of chiral vinyl ep-
oxides and the RCM reaction. We are currently refining
this strategy and developing syntheses of compounds 4
and 5 with the view of preparing croomine in the near
future.
(11) (1S,5S,7aS)-5-[(1S)-1-[[(1,1-Dimethylethyl)dimethyl-
silyl]oxy]-5-[(methoxyphenyl)methoxy]pentyl]-1-[3-[[(1,1-
dimethylethyl)dimethylsilyl]oxy]propyl]-5,7a-dihydro-
1H,3H-pyrrolo[1,2-c]oxazol-3-one (14): The diene 13 (547
mg, 0.826 mmol) was dissolved in anhyd CH2Cl2 (95 mL),
then Grubbs’ 1st generation catalyst (338 mg, 0.413 mmol)
was added. The mixture was heated at reflux under N2 for 7
d then cooled, before all volatiles were removed in vacuo to
give a black oil. The pure product was obtained by column
chromatography (increasing polarity from 10% to 40%
EtOAc in pet. sp. as eluant), which gave a black oil. This was
dissolved in EtOAc (30 mL) and stirred with activated
charcoal for 20 min to remove residual ruthenium, then
filtered through celite. Evaporation of the filtrate afforded
the title compound (485 mg, 0.785 mmol, 92.6%) as a
colorless oil. [a]D26 –86 (c = 1.0, CHCl3). MS (ES+): m/z
(%) = 634.5 (100) [M + 1]. HRMS (ES+): m/z [M + 1] calcd
for C34H59NO6Si2: 634.3959; found: 634.3975. 1H NMR
(300 MHz, CDCl3): d = 0.04 [s, 6 H, (CH3)2Si], 0.05 [s, 6 H,
(CH3)2Si], 0.86 [s, 9 H, (CH3)3CSi], 0.89 [s, 9 H, (CH3)3CSi],
1.34–1.96 (m, 10 H, H2¢, H3¢, H4¢, H1¢¢, H2¢¢), 3.44 (t, J =
6.6 Hz, 2 H, H5¢), 3.62–3.74 (m, 3 H, H1¢, H3¢¢), 3.79 (s, 3
H, OCH3), 4.24–4.30 (m, 1 H, H7a), 4.35 (q, J = 6.0 Hz, 1 H,
H1), 4.42 (s, 2 H, OCH2Ar), 4.54 (app. t, J = 3.9 Hz, 1 H,
H5), 5.85–5.92 (m, 2 H, H6, H7), 6.86 (d, J = 8.7 Hz, 2 H, 2
× ArCH), 7.25 (d, J = 8.7 Hz, 2 H, 2 × ArCH). 13C NMR (75
Acknowledgment
We thank the University of Wollongong for a PhD scholarship to
KBL and the Australian Research Council for financial support
References
(1) Pilli, R. A.; Ferreira de Oliveira, M. C. Nat. Prod. Rep. 2000,
17, 117.
(2) Mungkornasawakul, P.; Pyne, S. G.; Jatisatienr, A.; Supyen,
D.; Lie, W.; Ung, A. T.; Skelton, B. W.; White, A. H. J. Nat.
Prod. 2003, 66, 980.
(3) Kaltenegger, E.; Brem, B.; Mereiter, K.; Kalchhauser, H.;
Kählig, H.; Hofer, O.; Vajrodaya, S.; Greger, H.
Phytochemistry 2003, 63, 803.
(4) (a) Williams, D. R.; Brown, D. L.; Benbow, J. W. J. Am.
Chem. Soc. 1989, 111, 1923. (b) Chen, C. Y.; Hart, D. J. J.
Org. Chem. 1990, 55, 6236. (c) Chen, C. Y.; Hart, D. J. J.
Synlett 2004, No. 5, 779–782 © Thieme Stuttgart · New York

782
K. B. Lindsay, S. G. Pyne
LETTER
(13) (3S,9S,9aS)-3-[(1S)-1,4-Dihydroxybutyl]-9-hydroxy-1H-
MHz, CDCl3): d = –5.4 [q, (CH3)2Si], –4.6 (q, CH3Si), –4.4
(q, CH3Si), 18.0 [s, (CH3)3CSi], 18.3 [s, (CH3)3CSi], 22.2 (t,
C3¢), 25.8 [q, (CH3)3CSi], 25.9 [q, (CH3)3CSi], 27.9, 29.9,
31.9, 33.6 (t, C2¢, C4¢, C1¢¢, C2¢¢), 55.2 (q, OCH3), 62.3 (t,
C3¢¢), 70.0 (t, C5¢¢), 70.6 (d, C7a), 71.0 (d, C5), 72.5 (t,
OCH2Ar), 73.3 (d, C1'), 82.0 (d, C1), 113.7 (d, 2 × ArCH),
129.2 (d, 2 × ArCH), 129.6, 132.2 (d, C6 and C7), 130.8 (s,
ArC), 159.0 (s, ArC), 162.4 (s, C3).
pyrrolo[1,2-a]azepine (20): The tri-O-silyl ether 19 (61 mg,
0.0636 mmol) was dissolved in CHCl3 (0.5 mL), then MeOH
(4.0 mL) and concd HCl (1.0 mL, 38% w/w) were added.
The mixture was heated in a sealed tube at 90 °C for 3 d and
then cooled. The mixture was poured into Et2O (40 mL) and
extracted with 1 M HCl (3 × 15 mL). The combined aqueous
extracts were evaporated to dryness in vacuo to give a gum.
This was dissolved in water (2 mL) and applied to basic ion
exchange resin (OH form). Elution with water (50 mL) and
evaporation of the eluant gave the title compound (13 mg,
0.0534 mmol, 83.9%) as a pale brown gum. [a]D22 –34 (c =
1.3, MeOH). MS (CI+): m/z (%) = 244(100) [M + 1]. HRMS
(CI+): m/z [M + 1] calcd for C13H26NO3: 244.1913; found:
244.1916. 1H NMR (300 MHz, CDCl3): d = 1.30–2.10 (m,
17 H, H1, H2, H6, H7, H8, H2¢, H3¢, 2 × OH), 2.85 (ddd,
J = 12.3, 6.3, 2.4 Hz, 1 H, H5a), 2.94–3.08 (m, 2 H, H3,
H5b), 3.29 (td, J = 6.9, 2.4 Hz, 1 H, H9a), 3.38 (ddd, J = 9.0,
6.3, 2.4 Hz, 1 H, H1¢), 3.60–3.76 (m, 2 H, H4¢), 3.94 (br d,
J = 6.9 Hz, 1 H, H9). 13C NMR (75 MHz, CDCl3): d = 22.9
(t, C7), 27.9, 28.9, 29.4, 30.1, 32.1, 34.8 (t, C1, C2, C6, C8,
C2¢, C3¢), 52.5 (t, C5), 62.9 (t, C4¢), 65.3 (d, C9a), 71.0 (d,
C3), 72.6 (d, C9), 72.8 (d, C1¢).
(12) (3S,9S,9aS)-9-[[(1,1-Dimethylethyl)diphenylsilyl]oxy]-3-
[(1S)-1,4-bis[[(1,1 dimethylethyl)diphenylsilyl]oxy]-butyl]-
1H-pyrrolo[1,2-a]azepine (19): The amino alcohol 18 (727
mg, 0.744 mmol) was dissolved in CH2Cl2 (60 mL), then the
solution was cooled to 0 °C. Carbon tetrabromide (604 mg,
1.828 mmol) and triphenylphosphine (475 mg, 1.828 mmol)
were added, then the mixture was stirred at 0 °C for 10 min,
before Et3N (3.70 g, 36.56 mmol) was added. The mixture
was stirred at 0 °C for 5 h, then left to stand at 4 °C for 20 h,
then stirred at r.t. for 24 h. The mixture was poured into
water (50 mL) and extracted with CH2Cl2 (3 × 20 mL). The
combined organic extracts were dried (MgSO4), filtered and
evaporated to give a black semi-solid. The pure products
were obtained by column chromatography (increasing
polarity from 5% to 25% EtOAc in petroleum spirit as
eluant), which gave the title compound (451 mg, 0.470
mmol, 63.2%) and the partially stable bromide intermediate.
The bromide intermediate was dissolved in CH2Cl2 (10 mL)
and Et3N (5 mL), then heated at reflux for 3 h. Work up and
column chromatography as described above gave further
title compound (128 mg, 0.134 mmol, 17.9%, total yield
81.1%) as a colorless oil. [a]D24 –35 (c =1.28, CHCl3). MS
(ES+): m/z (%) = 958.6(100) [M + 1]. HRMS (ES+): m/z [M
+ 1] calcd for C61H80NO3Si: 958.5446; found: 958.5452. 1H
NMR (300 MHz, CDCl3): d = 1.07 [s, 9 H, (CH3)3Csi], 1.11
[s, 1 8 H, (CH3)3Si], 0.80–1.80 (m, 13 H, H1, H2, H6, H7,
H8a, H2¢, H3¢), 1.84–2.00 (m, 1 H, H8b), 2.34 (dd, J = 13.2,
9.0 Hz, 1 H, H7a), 2.55 (dd, J = 13.5, 6.6 Hz, 1 H, H7b),
3.10–3.20 (m, 1 H, H9a), 3.28–3.36 (m, 1 H, H5), 3.50 (t,
J = 6.0 Hz, 2 H, H4¢), 3.76–3.84 (m, 1 H, H9), 3.84–3.92 (dd,
J = 7.2, 3.0 Hz, 1 H, H1¢), 7.28–7.44 (m, 18 H, SiPh), 7.58–
7.73 (m, 12 H, SiPh). 13C NMR (75 MHz, CDCl3): d = 19.2
[s, (CH3)3CSi], 19.3 [s, (CH3)3CSi], 19.5 [s, (CH3)3CSi],
26.8 [q, (CH3)3CSi], 27.1 [q, (CH3)3CSi], 27.2 [q,
(14) (3S,5S,9S,9aS)-3-[(5S)-tetrahydro-5-oxo-2-furanyl]-5,9-
epoxy-1H-pyrrolo[1,2-a]azepine (22): The triol 20 (25 mg,
0.103 mmol) was dissolved in HOAc (2 mL), then TEMPO
(5 mg, 0.032 mmol) and BAIB (113 mg, 0.35 mmol) were
added. The mixture was stirred at r.t. for 24 h, then
Na2S2O3·5H2O (125 mg, 0.504 mmol) was added. After 20
min the mixture was poured into 5% NH4OH solution (40
mL) and extracted with CH2Cl2 (3 × 20 mL). The combined
organic extracts were dried (MgSO4) filtered and evaporated
in vacuo to give an oil. The pure product was obtained by
column chromatography (2% MeOH in CH2Cl2 as eluant),
which gave the title compound (7 mg, 0.029 mmol, 28.6%)
as a pale yellow semi solid. MS (CI+): m/z (%) = 238 (100)
[M + 1]. 1H NMR (300 MHz, CDCl3): d = 0.80–2.00 (m, 10
H, H1a, H2, H6, H7, H8, H4¢a), 2.00–2.14 (m, 1 H, H1b),
2.25 (dddd, J = 12.6, 8.1, 6.9, 5.7 Hz, 1 H, H4¢b), 2.53 (dd,
J = 9.6, 3.3 Hz, 1 H, H3¢a), 2.55 (dd, J = 9.6, 0.9 Hz, 1 H,
H3¢b), 3.02 (ddd, J = 10.2, 7.5, 5.4 Hz, 1 H, H3), 3.46–3.80
(m, 1 H, H9a), 4.02 (d, J = 1.5 Hz, 1 H, H9), 4.37 (dt, J = 7.8,
7.2 Hz, 1 H, H5¢), 4.82 (s, 1 H, H5). 13C NMR (75 MHz,
CDCl3): d = 16.8 (t, C7), 25.4 (t, C4¢), 28.8 (t, C3¢), 28.9,
29.2 (t, C6, C8), 31.5 (t, C2), 31.6 (t, C1), 68.7 (d, C9a), 70.9
(d, C3), 78.9 (d, C9), 85.3 (d, C5¢), 96.0 (d, C5), 177.0 (s,
C2).
(CH3)3CSi], 25.0, 25.1, 26.2, 27.1, 28.1, 30.0, 34.1 (t, C1,
C2, C6, C7, C8, C2¢, C3¢), 48.3 (t, C7), 64.2 (t, C4¢), 66.2 (d,
C3), 66.7 (d, C9a), 74.0 (d, C9), 76.5 (d, C1¢), 127.4, 127.5,
129.4, 129.5 (d, SiPh), 134.2, 134.2, 134.2, 134.5, 134.6,
134.7 (s, SiPh), 136.0, 136.0, 136.0 (d, SiPh).
(15) (a) De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974. (b) Paterson,
I.; Tudge, M. Angew. Chem. Int. Ed. 2003, 42, 343.
Synlett 2004, No. 5, 779–782 © Thieme Stuttgart · New York